Early prediction of subsequent molecular response to nilotinib in patients with chronic myeloid leukemia: Comparison of the quantification of BCR-ABL1 ratios using ABL1 or GUSB control genes.

ABSTRACT The molecular monitoring of BCR-ABL1 transcripts is a critical prognostic indicator of treatment response in chronic myeloid leukemia (CML). The quantification of BCR-ABL1 transcripts using ABL1 or GUSB as control genes on the early molecular response (MR) to front-line nilotinib was studied using data from 60 patients with chronic phase CML from the ENEST1st substudy. The impact of BCR-ABL1/ABL1 and BCR-ABL1/GUSB ratios at early timepoints as independent variables on subsequent MR was determined by logistic regression analyses and predictive cut-off values determined by receiver operating curve analyses (ROC). From day 45 there was correlation between early transcript kinetics and concordance between both control genes’ ability to predict subsequent MR4 at 18 months. From baseline to 3 months, transcripts descended linearly with both control genes. The use of ABL1 allowed for an earlier prediction (2 months) of subsequent MR than GUSB (3 months), with cut-off values of 1.5% and 0.19%, respectively. The dynamic determination of BCR-ABL1 transcripts using either internal control gene is valid and predictive of subsequent MR. These results do not support the use of GUSB for the prediction of an earlier response with more accuracy than ABL1. Accurate early indicators of MR are essential to identify patients likely to have inferior outcomes who may benefit from treatment with an alternative tyrosine kinase inhibitor.